This is a two-part, multicenter, multiple-country, randomized, double-blinded, placebo-controlled study in early-stage Parkinson’s Disease (PD) patients carrying a GBA mutation.
The purpose of this study is to evaluate the possible risks and the effectiveness of GZ/SAR402671 (study medication) once daily compared to placebo in the treatment of PD patients carrying a specific type of gene mutation, called the GBA (glucocerebrosidase) mutation.
GZ/SAR402671 has never been tested in patients with Parkinson’s disease, including Parkinson’s patients who have mutations in genes (such as the glucocerebrosidase gene, GBA). Research by other people indicates that GBA is a genetic risk factor for PD. Based on this research, it is believed that PD patients with a GBA mutation (GBA-PD) have an associated reduction in a brain protein that leads to an increase in the levels of a lipid component in brain cells It is thought that increases in this lipid component in the brain may disrupt normal brain functioning and lead to motor problems (for example, shaking hands, stiff muscles, short steps, poor balance, and falls) and nonmotor problems (for example, sleep, memory, long term attention, and ability to plan hard tasks).
The study is divided into 2 consecutive parts: Part 1 determined the selection of the dose of GZ/SAR402671 for Part 2. Part 1 is complete. Only Part 2 is being done at Legacy.
Part 2 will include 4 main periods:
Period 1 – up to 45-day screening period
At the screening visit, after the consent has been signed, one blood sample will be collected for investigation of GBA mutations. This gene will be sequenced even if historical results are available. Also, this sample will be investigated for a specific mutation in the LRRK2 gene (G2019S) and patients carrying this mutation will be excluded. Once the results of the GBA gene sequencing (positive for a GBA mutation) and the LRRK2 genotyping (negative for the G2019S mutation) are confirmed, the remaining of the screening activities can continue.
Period 2 - 52-week blinded treatment period
Period 3 - 104-week duration long-term follow-up (LTFU) If subjects complete the 52 weeks of double-blinded treatment, they may be eligible to transition to the LTFU period where, at some point, they will receive GZ/SAR402671 treatment, but they will not know what type of study medication they are taking or when it may change from placebo to GZ/SAR402671.
Period 4 - the 6-week post-treatment observation period
Subjects will be taking a capsule once daily.